When active ingredients are therapeutically administered to a patient, they are often contained in a carrier. In the context of tissue repair, demineralized bone powder is often used as the active ingredient to induce new bone growth at a bone defect site. Demineralized bone powder can be a loose, powdery material that is not easily contained at a bone defect site, particularly in the presence of body fluids and surgical irrigation. Therefore, demineralized bone powder may be combined with a carrier in order to provide a composition with improved handling characteristics and the ability to stay in place at the bone defect site for a sufficient amount of time to effect new bone growth.
Demineralized bone powder is a material that can be prepared by conventional procedures. Demineralized bone powder is generally composed of particles of bone tissue that have been specially treated, generally by soaking in acid, to remove their mineral content. The resulting demineralized bone powder is composed mainly of highly cross-linked collagen. The remaining non-collagenous proteins include proteins such as TGF-β, PDGF, osteopontin, osteonectin, bone morphogenetic proteins (BMPs), and others. BMPs are a group of proteins categorized in the transforming growth factor beta super-family of proteins.
Isolated BMPs are another material that can induce the formation of new bone and that can be prepared by conventional procedures. To date, several BMPs have been isolated and associated with the bone healing process. BMPs can be isolated from bone as a mixture of proteins or produced individually through recombinant gene technology.
Demineralized bone powder and BMPs have been combined with carriers to produce bone repair compositions. Jefferies (U.S. Pat. No. 4,394,370) discloses tissue repair compositions containing demineralized bone powder, BMPs, or both in a reconstituted collagen matrix. Glowacki et al. (U.S. Pat. No. 4,440,750) discloses aqueous compositions of demineralized bone particles and reconstituted collagen fibers.
Clokie (U.S. Pat. No. 6,309,659) describes a biocompatible connective tissue repair composition comprising bone powder and a carrier of poloxamer 407 (also known as Pluronic® F127, manufactured by BASF Corporation) and water. Pluronic® F127 is a polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer of the formula:
wherein a is about 101 and b is about 56. This molecule has two hydroxyl groups (—OH), one at each of the far ends of the long polymeric molecule. At particular concentrations and temperatures, a composition of Pluronic F127 and water exhibits reverse phase thermal characteristics in that it can form a gel and become increasingly viscous or solidified as its temperature increases.
Shimura et al. (International Patent Application No. WO97/18829) describes a composition that contains a polyoxyethylene-polyoxypropylene glycol (e.g., ADEKA® F127) and a bone morphogenetic protein, and reportedly displays a reverse phase characteristic.
There is a continuing need in the art for carriers for active ingredients and, in particular, for carriers to be used in tissue repair compositions.